This is a proposal to establish high throughput DNA sequencing technology at the University of Rochester. The University has a rich portfolio of NIH-funded research that would benefit from access to high throughput DNA sequencing. Diverse projects, ranging from genome analysis in caries-causing bacteria to mapping of long QT alleles in patients with hereditary heart conditions, will address questions with direct impact on human health. Further projects include research on oncogene cooperation, metabolic regulation, signal transduction, gene regulation and epigenetics. The PIs of many of these projects are internationally recognized leaders in their fields and publish their work in the journals of the highest impact. In addition, the Nasonia (a parasitic wasp) genome project, a multi-campus effort that is coordinated by scientists at the University of Rochester would benefit substantially from this technology. Moreover, mathematical and statistical teams with experience in bioinformatics and biostatics will develop and refine innovative tools for the application of high throughput sequencing technology to biomedical research. The requested instrument is an Illumina Genome Analyzer II. It will be housed in the established functional genomics core facility (FGC). A full-time dedicated staff member of the FGC will run the instrumentation. Staff of the FGC will also provide user assistance with data processing and analysis. More advanced computational support will be available through the newly inaugurated University of Rochester Center for Research Computing (CRC), which houses several high performance computing and large data storage resources. The staff of the CRC includes programmers and informaticians with expertise in genomics, who will be available to assist users with the analysis of large scale DNA sequence data. Institutional support and oversight will be provided for the running of the instrument. The extension of genomic core services to include high throughput sequencing is an integral part of the strategic plan of the University of Rochester, which projects a significant expansion of genomics research over the coming four years. This strategic plan includes the recruitment of ten new faculty members in the areas of genomics, systems biology, and bioinformatics. In addition, undergraduate and graduate teaching in bioinformatics and genomics will be expanded.